Obeticholic acid has the chemical name (3α,5β,6α,7α)-6-ethyl-3,7-dihydroxycholan-24-oic acid. Obeticholic acid has the following chemical structure:

Obeticholic acid (abbreviated to OCA) is a semi-synthetic bile acid analogue which has the chemical name 6α-ethyl-chenodeoxycholic acid. Obeticholic acid is a Farnesoid X receptor agonist indicated for primary biliary cholangitis/cirrhosis (PBC) and being developed by Intercept Pharmaceuticals Inc. for the treatment of other liver conditions such as Non-alcoholic steatohepatitis (NASH).
Obeticholic acid is known from U.S. Pat. No. 7,138,390.
Obeticholic acid salts are known from U.S. Pat. No. 9,732,117, CZ 2016-222, WO 2016/046680, WO2017137931, and US20180099991.
Crystalline forms of obeticholic acid, a pharmaceutical composition comprising obeticholic acid Form 1 (non-crystalline form of obeticholic acid) and a pharmaceutically acceptable carrier, wherein the obeticholic acid Form 1 comprises less than 1% of chenodeoxycholic acid are described in U.S. Pat. No. 9,238,673.
(S)-α-methylbenzylamine and diethylamine salt of obeticholic acid and process for preparation of amorphous form by conversion of the salt to amorphous form of obeticholic acid are known from WO2017/137931. Obeticholic acid-Ursodeoxycholic acid cocrystal and obeticholic acid monoammonium salt are known from WO2018165269.
Polymorphism, the occurrence of different crystal forms, is a property of some molecules and molecular complexes. A single compound, like obeticholic acid or salt thereof, may give rise to a variety of polymorphs having distinct crystal structures and physical properties like melting point, thermal behaviors (e.g. measured by thermogravimetric analysis—“TGA”, or differential scanning calorimetry—“DSC”), powder X-ray diffraction (PXRD) pattern, infrared absorption fingerprint, Raman absorption fingerprint, and solid state (13C-) NMR spectrum. One or more of these techniques may be used to distinguish different polymorphic forms of a compound.
Different salts and solid state forms (including solvated forms) of an active pharmaceutical ingredient may possess different properties. Such variations in the properties of different salts and solid state forms and solvates may provide a basis for improving formulation, for example, by facilitating better processing or handling characteristics, improving the dissolution profile, or improving stability (polymorph as well as chemical stability) and shelf-life. These variations in the properties of different salts and solid state forms may also provide improvements to the final dosage form, for instance, if they serve to improve bioavailability. Different salts and solid state forms and solvates of an active pharmaceutical ingredient may also give rise to a variety of polymorphs or crystalline forms, which may in turn provide additional opportunities to use variations in the properties and characteristics of a solid active pharmaceutical ingredient for providing an improved product.
Discovering new salts, solid state forms and solvates of a pharmaceutical product can provide materials having desirable processing properties, such as ease of handling, ease of processing, storage stability, and ease of purification or as desirable intermediate crystal forms that facilitate conversion to other salts or polymorphic forms. New salts, polymorphic forms and solvates of a pharmaceutically useful compound can also provide an opportunity to improve the performance characteristics of a pharmaceutical product (dissolution profile, bioavailability, etc.). It enlarges the repertoire of materials that a formulation scientist has available for formulation optimization, for example by providing a product with different properties, e.g., a different crystal habit, higher crystallinity or polymorphic stability which may offer better processing or handling characteristics, improved dissolution profile, or improved shelf-life.
In case of obeticholic acid, there are several known impurities. Therefore, there is a need for crystalline salt of obeticholic acid, useful in purification of obeticholic acid and suitable for industrial process.